A relationship between high blood pressure and diabetes

Research team led by the universities of Bristol, UK, and Auckland, New Zealand, has finally solved the long-standing mystery of why so many individuals with high blood pressure (commonly known as hypertension) also have diabetes (high blood sugar).

The critical new finding revealed that glucagon-like peptide-1 (GLP-1) is a tiny protein cell that relates the body's control of blood sugar and blood pressure.

"We've known for a long time that hypertension and diabetes are inextricably linked and have finally discovered the reason, which will now inform new treatment strategies," said Professor Julian Paton, a senior author and Director of Manaaki Mnawa — The Centre for Heart Research at the University of Auckland.

Collaborating scientists from Brazil, Germany, Lithuania, and Serbia, as well as the United Kingdom and New Zealand, contributed to the study, which was published online ahead of print in Circulation Research [1 February].

After eating, GLP-1 is produced from the gut wall, which stimulates the pancreas to produce insulin, which helps to regulate blood sugar levels. This was previously known, however it has recently been discovered that GLP-1 also stimulates the carotid body, a tiny sensory organ in the neck.

The researchers at the University of Bristol employed RNA sequencing, an unbiased, high-throughput genomics approach, to read all the messages of the expressed genes in the carotid body of rats with and without high blood pressure. This led to the discovery that the GLP-1 receptor is found in the carotid body, but not as much in hypertensive rats.

Professor of Experimental Medicine and senior author David Murphy of Bristol Medical School: Translational Health Sciences (THS) explained: "The discovery of the association necessitated genetic profiling and many validation processes. We didn't expect GLP-1 to show up on the radar, so this is quite interesting and offers up a lot of new possibilities."

"The carotid body is the convergence point where GLP-1 functions to manage both blood sugar and blood pressure at the same time," Professor Paton explained. "This is coordinated by the neurological system, which is guided by the carotid body."

Hypertensive and diabetic patients are at a higher risk of developing life-threatening cardiovascular disease. A considerable number of individuals will remain at high risk even after getting treatment. This is because most drugs simply address the symptoms of high blood pressure and diabetes, not the underlying reasons.

"We've known that blood pressure is notoriously difficult to control in patients with high blood sugar," said Professor Rod Jackson of the University of Auckland, "so these findings are really important because by giving GLP-1 we might be able to reduce both sugar and pressure together, and these two factors are major contributors to cardiovascular risk."

"The prevalence of diabetes and hypertension is increasing throughout the world, and there is an urgent need to address this," said Mr Audrys Paua, a British Heart Foundation-funded PhD student in Professor David Murphy's group at the Bristol Medical School and the study's principal author.

"Drugs that target the GLP-1 receptor have previously been licenced for human use and are often used to treat diabetes." These medicines, in addition to lowering blood sugar, also lower blood pressure, albeit the mechanism of this effect is unknown.

"This study found that these medications may have an anti-hypertensive impact through acting on the carotid bodies." As a result of this research, we're already preparing human translational trials to put what we've learned into reality so that the most vulnerable patients can get the best therapy possible."

But GLP-1 is only the beginning. The study has uncovered a slew of new targets for ongoing functional studies, which the researchers hope will lead to future translational initiatives in hypertensive and diabetic patients.

Reference:

Audrys G. Pauza, Pratik Thakkar, Tatjana Tasic, Igor Felippe, Paul Bishop, Michael P. Greenwood, Kristina Rysevaite-Kyguoliene, Julia Ast, Johannes Broichhagen, David J. Hodson, Helio C. Salgado, Dainius H. Pauza, Nina Japundzic-Zigon, Julian F.R. Paton, David Murphy. GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition. Circulation Research, 2022; DOI: 10.1161/CIRCRESAHA.121.319874